- The US drug major Eli Lilly has filed a patent infringement litigation at the Delhi High Court against several Indian pharmaceutical companies for the intellectual property rights on its drug Baricitinib, for allegedly marketing and advertising sale of Barinat – the brand name under which Hyderabad-based Natco manufactures and markets Baricitinib – as a treatment for rheumatoid arthritis.
- The company has issued eight royalty-free voluntary licenses to Indian pharmaceutical companies to distribute the drug solely for the treatment of Covid-19, a few months back. Eli Lilly sells the drug under the brand Olumiant.
- Baricitinib – Active patents – IN270765 (1863/MUMNP/2010) – Expected expiry date: 10/03/2029 covering Baricitinib free base and Baricitinib Phosphoric acid API.
Eli Lilly is fighting a patent infringement litigation against several Indian companies for the intellectual property rights on its compound Baricitinib, even though it has issued eight royalty-free voluntary licenses to Indian pharmaceutical companies to distribute the drug solely for treatment of Covid-19, a few months back. Eli Lilly sells the drug under the brand Olumiant.
The company has filed a complaint at the Delhi High Court against almost 20 entities or individuals for allegedly marketing and advertising sale of Barinat – the brand name under which Hyderabad-based Natco manufactures and markets Baricitinib – as a treatment for rheumatoid arthritis. Eli Lilly announced in May this year that it has entered into a royalty-free voluntary license agreement with Natco, only for the treatment of Covid-19.
Eli Lilly argued that the alleged marketing and advertising of the product for another ailment is “a clear breach of the license granted by the company to Natco, which permitted marketing of Baricitinib, by Natco, only for the treatment of Covid-19”. In May, the US drug major received Emergency Use Approval (EUA) for the use of the drug in combination of Remdesivir, for treatment of Covid-19.
Following this, the company entered into a voluntary license agreement with Indian pharmaceutical companies including Natco to distribute the compound under their individual trademark/brand names, solely for the purpose of treatment of Covid-19. The license did not permit the export of the drug or marketing of the drug for treatment of any ailment other than Covid-19.
According to reports, Eli Lilly has issued royalty-free voluntary licenses to Indian players including Sun Pharma, Cipla, Lupin and Torrent. Bajaj Healthcare, another Indian player, approached the Indian Patent authority seeking compulsory licensing for the drug, after Eli Lilly denied voluntary licensing to the company, said reports.
Baricitinib is authorised for use under an Emergency Use Authorization (EUA) for treatment of Covid-19 in hospitalised adults and pediatric patients two years of age or older requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
Natco, acknowledging that the license granted was only for marketing of the drug to treat Covid-19, submitted to the Court that it has no objection if the Court injunction marketing and sale of Barinat for any purpose other than the treatment of Covid-19, as well as for export.
The company said that it has not breached the agreement with Eli Lilly, which the latter also agreed. Eli Lilly said that the cause of action in the complaint is not directed against Natco, but against the entities which are marketing Natco’s product for treatment of rheumatoid arthritis. The Court, following this, in September, granted an interim injunction restraining 20 defendants from marketing or selling Barinat, in any form except for the treatment of Covid-19, on any virtual platform or physically across the counter, apart from export till next hearing.
In a hearing held on November 15, one of the defendants – Bull Pharmachem – has submitted that the marketing or display of Barinat as a treatment for rheumatoid arthritis was an inadvertent error of the marketing team and that it had no intention of selling the drug as a treatment for rheumatoid arthritis or for which it was not produced. It has not sold the drug as a treatment for rheumatoid arthritis, it added.
The company said that it would not market or sell the drug as treatment for any ailment other than Covid-19 and would not export the tablets. Justice C Hari Shankar, in his order, observed that no cause of action survives against Bull Pharma after the undertaking and ordered that it shall not continue to be treated as in the array of parties.
Eli lilly signed royalty-free, non-exclusive voluntary licensing agreement with following companies:
On May 10, 2021
Sun Pharmaceutical Industries Ltd. (Reuters: SUN.BO, Bloomberg: SUNP IN, NSE: SUNPHARMA, BSE: 524715, “Sun Pharma” and includes its subsidiaries and/or associate companies) announced that it has entered into a royalty-free, non-exclusive voluntary licensing agreement with Eli Lilly and Company (“Lilly”) for expanding access to Lilly’s drug, baricitinib in India. Sun Pharma will manufacture and distribute the drug in India.
Kirti Ganorkar, CEO-India business, Sun Pharma, said, “Through this collaboration, we aim to join our forces with Lilly to accelerate access to baricitinib in India at a time when it is most needed. This is another step by Sun Pharma towards making more treatment options available to patients in India for dealing with the pandemic.”
On May 10, 2021
Global pharma major, Lupin Limited (Lupin) announced that it has signed a royalty-free, limited, non-exclusive voluntary licensing agreement with Eli Lilly and Company (Lilly) for manufacturing and selling of Lilly’s drug Baricitinib in India.
On May 10, 2021
Pharma major Cipla Limited on announced that it has signed a royalty-free, non-exclusive voluntary licensing agreement with Eli Lilly and Company, USA, for the manufacturing and commercialization of rheumatoid arthritis drug Baricitinib for treatment of Covid-19 patients.
Cipla said this collaboration is a step further in the company’s efforts to enhance access to critical treatments for patients affected by the pandemic. Cipla will leverage its extensive distribution footprint to make this therapy accessible to more patients and markets.
On May 13, 2021
Hyderabad-based MSN Labs (MSN) said it has entered into a royalty-free, non-exclusive, voluntary license agreement with US drug giant Eli Lilly & Co for manufacturing and marketing Covid-19 treatment drug Baricitinib in India.
MSN Labs has joined a small, but growing list of drugmakers in India with whom US pharma giant Eli Lilly has got into royalty free, non-exclusive, voluntary license agreements for manufacture and marketing of Baricitinib, a drug used to treat COVID-19.
On May 13, 2021
Torrent Pharmaceuticals Limited on Thursday announced that it has entered into a voluntary licensing agreement with Eli Lilly and Company to make the Covid-19 drug baricitinib in India. Under the royalty-free, non-exclusive voluntary licensing agreement, Eli Lilly has provided the license to manufacture and distribute baricitinib to Torrent for India along with Lilly’s other license partners.
According to Torrent Pharma’s chief marketing officer Aman Mehta, the agreement will help ensure wider reach and access to patients in India and further adds to Torrent Pharma’s effort in helping patients affected by the pandemic.
“This partnership further strengthens our efforts to help the nation fight the pandemic and provide quality treatment to patients. Torrent Group stands firmly committed to support the nation during this time of crisis,” Mehta added.
On May 17, 2021
Eli Lilly, announced that it had issued an additional royalty-free, non-exclusive voluntary license to Natco Pharma to manufacture and distribute Baricitinib in the country
In line with the agreement, Natco has withdrawn the application filed with the Indian Patent Office seeking Compulsory License against Lilly for Baricitinib for COVID-19 in India.
Earlier this month, Natco had received emergency use authorisation for Baricitinib tablets from the Central Drugs Standard Control Organisation (CDSCO). The drug is for use, in combination with Remdesivir, in treatment of suspected or laboratory confirmed COVID-19 in hospitalised adults requiring supplemental oxygen, invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). Following the EUA, it had also launched the product.
What is litigation?
Litigation is the process of taking a dispute to a court of law. If parties cannot agree between themselves about the fair and proper outcome of a dispute they will present their respective cases to a court for its judgment. It is a broad term that describes a long and sometimes complex process. In this article, we will break down the stages in the litigation process.
What kind of cases can be resolved using litigation?
There are a wide range of cases which can be resolved using litigation. These can include:
- Commercial disputes e.g. claims for breach of contract such as damaged goods or recovery of debts;
- Matrimonial matters e.g. determining the extent of a spousal claim in a divorce action;
- Claims against the state e.g. A judicial review of a planning decision;
- Personal injury claims e.g. monetary claims arising out of an accident where a person suffered harm;
- Employment disputes e.g. a claim for wrongful dismissal.
What is Baricitinib?
Baricitinib, sold under the brand name Olumiant among others, is a drug for the treatment of rheumatoid arthritis (RA) in adults whose disease was not well controlled by tumor necrosis factor (TNF) inhibitors. It acts as an inhibitor of janus kinase (JAK), blocking the subtypes JAK1 and JAK2. The drug is approved for medical use in the European Union and in the United States.An important side effect of JAK inhibitors is serious bacterial, mycobacterial, fungal and viral infections
Baricitinib in COVID-19:
In April 2020, Lilly announced they are investigating the use of Baricitinib for treating people with COVID-19. The drug’s anti-inflammatory activity is expected to act on the inflammatory cascade associated with COVID-19.
In November 2020, published research showed Barcitinib was beneficial in treating people with COVID-19. According to the paper “mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication and the cytokine storm, and is associated with beneficial outcomes including in severely ill elderly people”.
In a clinical trial of hospitalized people with COVID-19, Baricitinib, in combination with Remdesivir, was shown to reduce time to recovery within 29 days after initiating treatment compared to participants who received a placebo with Remdesivir. The safety and effectiveness of this investigational therapy for use in the treatment of COVID-19 continues to be evaluated.
The data supporting the US Food and Drug Administration (FDA) emergency use authorization (EUA) for baricitinib combined with remdesivir are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), which was conducted by the US National Institute of Allergy and Infectious Diseases (NIAID). This clinical trial evaluated whether baricitinib impacted how long it took for subjects who were also taking remdesivir to recover from COVID-19. The trial followed participants for 29 days and included 1,033 participants with moderate or severe COVID-19; 515 participants received baricitinib plus remdesivir, and 518 participants received placebo plus remdesivir. Recovery was defined as either being discharged from the hospital or being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care. The median time to recovery from COVID-19 was seven days for baricitinib plus remdesivir and eight days for placebo plus remdesivir. The odds of a patient’s condition progressing to death or being ventilated at day 29 was lower in the baricitinib plus remdesivir group versus the placebo plus remdesivir group. The odds of clinical improvement at day 15 was higher in the baricitinib plus remdesivir group versus the placebo plus remdesivir group. For all of these endpoints, the effects were statistically significant.The EUA was issued to Eli Lilly and Company.
In November 2020, the World Health Organization (WHO) updated its guideline on therapeutics for COVID-19 to include a conditional recommendation against the use of remdesivir, triggered by results from the WHO Solidarity trial.
In November 2020, the FDA issued an emergency use authorization (EUA) for the combination of baricitinib with remdesivir, for the treatment of suspected or laboratory confirmed COVID-19 in hospitalized people aged two years of age or older requiring supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
In July 2021, the FDA revised the EUA for baricitinib now authorizing it alone for the treatment of COVID-19 in hospitalized people aged two years of age or older requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Under the revised EUA, baricitinib is no longer required to be administered with remdesivir.
- Baricitinib – Active patents
- Title: Azetidine and cyclobutane derivatives as jak inhibitors
- PCT Application: WO2009114512 A1
- Assignee: Incyte Corporation (Licensee Eli Lilly & Company)
- Indian Patent Equivalent: Indian Patent: IN270765 (1863/MUMNP/2010)
- Filing date: 01/09/2010 Grant date: 22/01/2016
- Expected expiry date: 10/03/2029
- Comments: Baricitinib free base and Baricitinib Phosphoric acid API.
- Form 27: Patented invention is worked in India by way of importation of Olumiant® Tab 2 Mg, Olumiant® Tab 4 Mg, and Olumiant® physician samples from Spain.
- Licensing options: may be explored.
Other Medical Uses:
In February 2017, baricitinib was approved for use in the EU as a second-line therapy for moderate to severe active rheumatoid arthritis in adults, either alone or in combination with methotrexate.
On 31 May 2018, the FDA approved barictinib for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.
Mechanism of action (MOA):
Baricitinib is a Janus kinase (JAK) inhibitor that reversibly inhibits Janus kinase 1 with a half maximal inhibitory concentration (IC50) of 5.9 nM and Janus kinase 2 with an IC50 of 5.7 nM. Tyrosine kinase 2, which belongs to the same enzyme family, is affected less (IC50 = 53 nM), and Janus kinase 3 far less (IC50 > 400 nM). Via a signal transduction pathway involving STAT proteins, this ultimately modulates gene expression in immunological cells.
Other JAK inhibitors include tofacitinib, which is indicated for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis; fedratinib, and ruxolitinib
The substance is quickly absorbed from the gut with an absolute bioavailability of 79%. It reaches highest blood plasma levels after about an hour; in different individuals the time to reach this level ranges from 0.5 to 3 hours. Food intake has no relevant influence on the drug’s pharmacokinetics. 50% of the circulating baricitinib are bound to blood plasma proteins.
Less than 10% of the substance is metabolized to four different oxidation products by CYP3A4; the rest is left unchanged. Elimination half-life is 12.5 hours on average. About 75% is eliminated via the urine, and 20% via the faeces.
Eli Lilly and Company is an American pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 countries. The company was founded in 1876 by, and named after, Colonel Eli Lilly, a pharmaceutical chemist and veteran of the American Civil War.
About Eli Lilly:
Lilly’s notable achievements include being the first company to mass-produce the polio vaccine developed by Jonas Salk, and insulin. It was one of the first pharmaceutical companies to produce human insulin using recombinant DNA including Humulin (insulin medication), Humalog (insulin lispro), and the first approved biosimilar insulin product in the US, Basaglar (insulin glargine).
Lilly is currently the largest manufacturer of psychiatric medications and produces Prozac (fluoxetine), Dolophine (methadone), Cymbalta (duloxetine), and Zyprexa (olanzapine).
The company is ranked 123rd on the 2019 Fortune 500. It is ranked 221st on the Forbes Global 2000 list of the largest public companies in the world and 252nd on the Forbes list of America’s Best Employers. Eli Lilly is a full member of the Pharmaceutical Research and Manufacturers of America and the European Federation of Pharmaceutical Industries and Associations (EFPIA).
As of 1997, it was the largest corporation and the largest charitable benefactor in Indiana.
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